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Exploring new Probenecid-based carbonic anhydrase inhibitors: Synthesis, biological evaluation and docking studies.
Bioorg Med Chem. 2015 Sep 01; 23(17):5311-8.BM

Abstract

Novel Probenecid-based amide derivatives, incorporating different natural amino acids, were synthesized and assayed to test their effect on the human carbonic anhydrase (hCA, EC 4.2.1.1) transmembrane isoforms hCA IX and XII over the ubiquitous isoforms hCA I and II. Most of them presented a complete loss of hCA II inhibition (K(i)s > 10,000 nM) and strong inhibitory activity against hCA IX and XII in the nanomolar range with respect to the parent compound. A residual activity against hCA I was observed for some of them. These biological results have been explained by docking studies within the active sites of the four studied human carbonic anhydrases (with or without the zinc-bound water) and helped us to better comprehend the rationale behind the design of tertiary sulfonamide compounds as potent but atypical inhibitors of specific isoforms of human carbonic anhydrase.

Authors+Show Affiliations

Department of Pharmacy, 'G. D'Annunzio' University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy. Electronic address: a.mollica@unich.it.Department of Pharmacy, 'G. D'Annunzio' University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.Bezmialem Vakif University, Faculty of Pharmacy, Department of Pharmacology, Vatan Caddesi, 34093 Fatih, Istanbul, Turkey.Department of Pharmacy, 'G. D'Annunzio' University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.Dipartimento di Chimica, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.Department of Pharmacy, 'G. D'Annunzio' University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy; Università degli Studi di Firenze, Neurofarba Dept., Section of Pharmaceutical and Nutriceutical Sciences, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26264840

Citation

Mollica, Adriano, et al. "Exploring New Probenecid-based Carbonic Anhydrase Inhibitors: Synthesis, Biological Evaluation and Docking Studies." Bioorganic & Medicinal Chemistry, vol. 23, no. 17, 2015, pp. 5311-8.
Mollica A, Costante R, Akdemir A, et al. Exploring new Probenecid-based carbonic anhydrase inhibitors: Synthesis, biological evaluation and docking studies. Bioorg Med Chem. 2015;23(17):5311-8.
Mollica, A., Costante, R., Akdemir, A., Carradori, S., Stefanucci, A., Macedonio, G., Ceruso, M., & Supuran, C. T. (2015). Exploring new Probenecid-based carbonic anhydrase inhibitors: Synthesis, biological evaluation and docking studies. Bioorganic & Medicinal Chemistry, 23(17), 5311-8. https://doi.org/10.1016/j.bmc.2015.07.066
Mollica A, et al. Exploring New Probenecid-based Carbonic Anhydrase Inhibitors: Synthesis, Biological Evaluation and Docking Studies. Bioorg Med Chem. 2015 Sep 1;23(17):5311-8. PubMed PMID: 26264840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploring new Probenecid-based carbonic anhydrase inhibitors: Synthesis, biological evaluation and docking studies. AU - Mollica,Adriano, AU - Costante,Roberto, AU - Akdemir,Atilla, AU - Carradori,Simone, AU - Stefanucci,Azzurra, AU - Macedonio,Giorgia, AU - Ceruso,Mariangela, AU - Supuran,Claudiu T, Y1 - 2015/08/01/ PY - 2015/05/13/received PY - 2015/07/28/revised PY - 2015/07/29/accepted PY - 2015/8/13/entrez PY - 2015/8/13/pubmed PY - 2016/5/27/medline KW - Molecular modeling KW - Probenecid KW - Selective carbonic anhydrase IX inhibitors KW - Selective carbonic anhydrase XII inhibitors KW - Tertiary sulfonamides SP - 5311 EP - 8 JF - Bioorganic & medicinal chemistry JO - Bioorg. Med. Chem. VL - 23 IS - 17 N2 - Novel Probenecid-based amide derivatives, incorporating different natural amino acids, were synthesized and assayed to test their effect on the human carbonic anhydrase (hCA, EC 4.2.1.1) transmembrane isoforms hCA IX and XII over the ubiquitous isoforms hCA I and II. Most of them presented a complete loss of hCA II inhibition (K(i)s > 10,000 nM) and strong inhibitory activity against hCA IX and XII in the nanomolar range with respect to the parent compound. A residual activity against hCA I was observed for some of them. These biological results have been explained by docking studies within the active sites of the four studied human carbonic anhydrases (with or without the zinc-bound water) and helped us to better comprehend the rationale behind the design of tertiary sulfonamide compounds as potent but atypical inhibitors of specific isoforms of human carbonic anhydrase. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/26264840/Exploring_new_Probenecid_based_carbonic_anhydrase_inhibitors:_Synthesis_biological_evaluation_and_docking_studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(15)00650-1 DB - PRIME DP - Unbound Medicine ER -